The specific aims of the proposed experiments are to examine the potential differences between rats allowed extended access (6 hours) to cocaine self-administration and rats given the traditional short access (1 hour); in 1) locomotor sensitization, 2) cocaine- and cue-induced reinstatement of cocaine-seeking after withdrawal, 3) the differences in basal and stimulated glutamate and dopamine levels, 4) molecular changes that accompany cocaine self-administration, namely in glutamate transmission-related proteins such as AGS3, PSD-95, mGluR1/5, xCT, GluR1, GluR2/3, and the Homer proteins. Rats trained to self-administer cocaine will experience two weeks of withdrawal and will then be challenged with three doses of cocaine (3, 10, and 30 mg/kg IP) to examine both locomotor sensitization and the ability of cues and cocaine to elicit the reinstatement of cocaine-seeking. Two weeks after the last self-administration session, the basal levels of glutamate and the stimulated levels of glutamate and dopamine in the nucleus accumbens will be measured via microdialysis. At the same time point that these behavioral and neurochemical changes will be monitored, we will also look for changes in known molecular markers of addiction via immunoblots. [unreadable] [unreadable] [unreadable]